The biological role of psoriasin in breast tumorigenesis
Alteration of psoriasin (S100A7) has previously been identified in association with the transition from preinvasive to invasive breast cancer. In this thesis we examined the 'in vitro' and 'in vivo' effects of psoriasin in two cell line models: MCF10AT3B, a "normal" breast cell line derived from non-neoplastic fibrocystic breast tissue and MDA-MB-231, an invasive breast cancer cell line. We first developed stable transfectants, along with appropriate vector alone controls and studied them in ' in vitro' cell growth and invasion assays, as well assessed them ' in vivo' with respect to tumor growth, mitotic abundance and necrotic content. We found that psoriasin has no effect on in vitro cell growth and invasive behavior in "normal" MCF10AT3B and invasive MDA-MB-231 breast cancer cells. Although we could not establish the tumorigenic "normal" breast cell line MCF10AT3B into a Balb C nu/nu mouse model, we were successful in our attempts using the invasive breast cancer cell line MDA-MB-231. Data from these experiments confirmed that psoriasin does not alter tumor cell growth 'in vivo'. As well, we observed that mitotic abundance and the amount of necrosis is independent of the presence of psoriasin in invasive MDA-MB-231 breast cancer cells. These results propose that psoriasin behaves similarly in "normal" and breast cancer models, nevertheless, our previous data suggests a role in the events that govern breast cancer. Specifically, although there is no evidence suggesting that psoriasin alters cell growth and invasion directly, psoriasin may govern the progression of early breast cancer due to changes in adhesion or angiogenesis.